Mutation in coronavirus protein reduces its neurovirulence

Researchers have discovered that a mutation in a coronavirus protein slows the spread of the virus in the central nervous system and reduces its neurovirulence.

It is the first time that this phenomenon has been observed in the coronavirus family, which is responsible for one-third of common colds and is also suspected of being associated with the development or aggravation of neurological diseases such as multiple sclerosis, Alzheimer's disease, and encephalitis.

The discovery, which has just been published in the journal PLoS Pathogens.

.The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). Researchers compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract.

They identified one predominant mutation at amino acid 758 (from RRSR# G758 to RRSR#R758), which introduces a putative furin-like cleavage site. Authors show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein.

While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS.